We propose a Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) at the University of California, San Diego, Stroke Center (UCSD). The Core facilities and projects will meet SPOTRIAS target goals, increasing the number of thrombolytic-treated patients, particularly those treated within 2 hours following stroke. To achieve this, we offer 4 inter-related projects. 1) To find a simple, serum marker of acute stroke, we will characterize the free fatty acid (FFA) response in acute stroke patients, including the time course. We will determine whether FFA levels correlate with various stroke outcomes, and attempt to distinguish ischemia from common mimics. We will characterize the FFA response associated with effective thrombolysis. 2) To use hypotherrnia to prolong the time window for thrombolysis in a Phase 1 trial, by studying thrombolysis beginning 3 to 6 hours following stroke onset, combined with 24 hours of intravascular cooling. We hypothesize that hypothermia will be safe in such patients. We will proceed to a Phase 2 trial to show that hypothermia reduces hemorrhage rates and improves outcomes in 3 to 6 hour thrombolysis patients. 3) To use a non-invasive, bedside test---contrast enhanced transcranial ultrasoundmto identify vascular occlusion and perfusion defects before and after thrombolysis. We will test whether ultrasound may separate stroke from mimics, and identify potential treatment candidates from among patients with mild or fluctuating deficits presenting within 2 hours. 4) To determine whether novel broadband wireless Internet technology will allow UCSD Stroke Team faculty to direct thrombolysis at remote hospitals by placing audio/video consultation capability at remote Emergency Departments in San Diego. Acute consults may increase the number of 2-hour thrombolytic treatments. These projects are built on the core facilities of the UCSD Stroke Center, which include a nationally recognized stroke team, a training program, a data collection and statistical analysis unit, and a specimen collection and storage facility. All of the needed teams, collaborations, and facilities are in place. The SPOTRIAS program will allow us to enhance and initiate translational research that ultimately will benefit stroke patients by treating more patients under 2 hours, and finding ways to treat additional patients later.